P = 0.001). The corresponding 5-year OS estimates were 49%  and 57% , respectively . The corresponding 5-year LSS estimates were 54%  and 66% , respectively . This population-based registry analysis shows that patients with t-FL continue to have an inferior survival in the modern era and should be prioritized for enrollment in clinical trials.Population-based data comparing the outcomes of patients with transformed follicular lymphoma (t-FL) and de novo diffuse large B-cell lymphoma (DLBCL) are lacking. The objective of this study was to compare the survival of patients with t-FL and de novo DLBCL diagnosed in the United States between 2010–2018. We hypothesized that patients with t-FL would have an inferior survival compared to patients with de novo DLBCL. The study outcomes were relative survival (RS), overall survival (OS), and lymphoma-specific survival (LSS) compared between t-FL and de novo DLBCL. Flexible parametric survival models were used to estimate the study outcomes. There were 569 cases of t-FL and 44,706 cases of de novo DLBCL. Patients with t-FL had an estimated 5-year RS of 54% [95% confidence interval (CI), 49–59%) compared to 67%  for those with de novo DLBCL (adjusted hazard ratio, 1.29; 95% CI, 1.11–1.50; The online version contains supplementary material available at 10.1186/s40364-023-00525-1. The treatment of B-cell lymphomas has advanced considerably over the past decade. However, only a few studies have reported the survival of transformed follicular lymphoma (t-FL) during this time period. Hence, we sought to compare the outcomes of t-FL and de novo diffuse large B-cell lymphoma (DLBCL) in the US population. We hypothesized that patients with t-FL would have an inferior survival compared to patients with de novo DLBCL.We conducted a population-based, multiple cohort study of patients with t-FL and de novo DLBCL in the US using the Surveillance, Epidemiology, and End Results (SEER)-18 database. The SEER-18 database covers approximately 27.8% of the U.S. population based on the 2010 US Census. We included adults with FL who met the following inclusion criteria: (1) age 18–84 years at the time of diagnosis of FL, (2) diagnosed with FL between 2010–2014, (3) microscopic confirmation of their disease, and (4) FL was their first malignant primary tumor. The upper age limit was restricted to 84 years of age to allow for adequate follow-up time. We excluded individuals who met the following exclusion criteria: (1) diagnosed by autopsy or death certificate and (2) primary central nervous system (CNS) lymphomas. We identified patients with t-FL by following patients from their diagnosis of FL to their subsequent diagnosis of DLBCL through the end of 2018. All patients with t-FL had biopsy-proven rather than clinically suspected transformed disease.We included adults with de novo DLBCL who met the following inclusion criteria: (1) age 18–99 years at the time of diagnosis of DLBCL (2) diagnosed with DLBCL between 2010–2018, (3) microscopic confirmation of their disease, and (4) DLBCL was their first malignant primary tumor. We excluded individuals who met the following exclusion criteria: (1) diagnosed by autopsy or death certificate and (2) primary CNS lymphomas. FL and DLBCL were identified using the SEER Lymphoid Neoplasm Recode 2021 Revision variable. Primary CNS lymphomas were identified by using the International Classification of Disease for Oncology topology codes C700-701, C709-729, and C751-753. Patients with composite DLBCL and FL  were grouped with the de novo DLBCL patients by SEER.The study outcomes were relative survival (RS), overall survival (OS), and lymphoma-specific survival (LSS). RS was defined as the ratio of all-cause to expected survival following diagnosis of lymphoma. Expected survival was estimated by matching patients with lymphoma to those in the general population by age, sex, year, and race using data from SEER. OS was defined as the probability of death from any cause following diagnosis of lymphoma. LSS was defined as the probability of survival when lymphoma was considered the only possible cause of death. Covariates were age at diagnosis, year of diagnosis, sex, race , Ann Arbor stage (stage I-II and stage III-IV), B symptoms, and geographic region . Age and year were modelled as continuous variables using restricted cubic splines with 3 knots. Age was also treated as a binary variable for specific analyses (< 65 years and ≥ 65 years).P-values less than 0.05 were considered significant. Analyses were performed using Stata/IC version 16.1 .Patient characteristics were analyzed using descriptive statistics. Differences between categorical and continuous variables were tested using Pearson’s chi-squared test and the Wilcoxon rank-sum test, respectively. Median follow-up time was estimated using the reverse Kaplan–Meier method . The stuP = 0.001). The corresponding 5-year LSS estimates were 54%  and 66% , respectively . The corresponding 5-year OS estimates were 49%  and 57% , respectively . The estimated median OS for patients with t-FL was 4.6 years  compared to 8.8 years  for those with de novo DLBCL. Table SAmong the 12,038 patients with FL who were included in the study, 569 (4.7%) patients developed biopsy-confirmed histologic transformation (HT) at a median follow-up of 6.3 years. A total of 44,706 patients with de novo DLBCL were also included in the study. Table SWe found that patients with t-FL had significantly lower survival compared to those with de novo DLBCL diagnosed between 2010–2018. This difference in survival was significant across study outcomes. Our results show that patients with t-FL were more likely to die from lymphoma compared to de novo DLBCL, which was supported using both cause-specific and relative survival frameworks. The differences in survival were larger for younger patients and those with limited stage disease. These findings stand in contrast to those from smaller cohort studies that did not observe a difference in survival between patients with t-FL and de novo DLBCL –7. PossiThe cumulative incidence of biopsy-proven HT in our study was 4.7% 569/12,038). This was lower than the cumulative incidence of 5.5% (147/2652) reported by the National LymphoCare study [. This wade novo DLBCL group; however, the number of patients with composite disease would not be large enough to alter the main findings of this study.Our study is limited by the lack of granularity pertaining to the treatment and molecular data as well as information on variables necessary to calculate International Prognostic Index scores. As we did not have access to the month of diagnosis for each patient, we were also unable to estimate the exact time-to-transformation. Lastly, it could be possible that a small number of patients with composite FL and DLBCL were included in the . Patients with t-FL should be prioritized for clinical trials given the relatively inferior prognosis of these patients. Future observational studies should incorporate treatment information and molecular data to better understand the underlying mechanism driving the differential outcome of t-FL and de novo DLBCL observed in our study.In conclusion, this is the largest study ever reported for t-FL. This is also the first population-based study to compare the outcomes of t-FL and de novo DLBCLAdditional file 1: Supplementary Appendix. Table S1. Characteristics of adults diagnosed with de novo DLBCL and t-FL in the United States, SEER-18 database, 2010-2018. Table S2. Flexible parametric survival models for adults diagnosed with t-FL and de novo DLBCL in the United States, SEER-18 database, 2010-2018


Targeted potassium levels to decrease arrhythmia burden in high-risk patients with cardiovascular diseases trial” (POTCAST). Patients were given standard therapy and randomized (1:1) to an intervention that included guidance on potassium-rich diets, potassium supplements, and mineralocorticoid receptor antagonists targeting high-normal p-K levels (4.5-5.0 mmol/l). Echocardiography was done at baseline and after a mean follow-up of 44 days (SD 18) and the echocardiograms were analyzed for changes in GLS, mechanical dispersion, E/A, e’, and E/e’. At follow-up, mean difference in changes in p-K was 0.52 mmol/l , P<0.001 in the intervention group compared to controls. GLS was improved with a mean difference in changes of -1.0% , P<0.05 and e’ and E/e’ were improved with a mean difference in changes of 0.9 cm/s , P = 0.04 and ? 1.5 , P = 0.03, respectively. Thus, induced increase in p-K to the high-normal range improved indices of systolic and diastolic function in patients with low-normal to moderately reduced LVEF.Plasma potassium (p-K) in the high-normal range has been suggested to reduce risk of cardiovascular arrythmias and mortality through electrophysiological and mechanical effects on the myocardium. In this study, it was to investigated if increasing p-K to high-normal levels improves systolic- and diastolic myocardial function in patients with low-normal to moderately reduced left ventricular ejection fraction (LVEF). The study included 50 patients (mean age 58 years (SD 14), 81% men), with a mean p-K 3.95 mmol/l (SD 0.19), mean LVEF 48% (SD 7), and mean Global Longitudinal Strain (GLS) -14.6% (SD 3.1) patients with LVEF 35–55% from “The online version contains supplementary material available at 10.1007/s10554-023-02914-x. Low as well as high plasma-potassium (p-K) levels have been shown to be associated with reduced survival . This maMyocardial function at low p-K levels has been studied experimentally in dogs (n = 27) and in healthy human volunteers n = 10) , 10. In  , 10. In2D-speckle tracking echocardiography has been demonstrated to be a sensitive and robust method for detection of subtle systolic dysfunction as in preclinical heart failure –18. FurtTargeted potassium level to decrease arrhythmia burden in high-risk patients with cardiovascular diseases (POTCAST) trial . The design of the POTCAST trial has been described previously [2, pregnancy, seeking pregnancy, or lack of ability to provide informed consent.The current substudy was prespecified in the protocol for the eviously . In brieeviously , 22 to eFor the present study, 50 consecutive patients from the POTCAST trial with LVEF between 35 and 55% were included between June 1, 2020 and May 31, 2021. Patients were excluded from the final analysis if any of the following criteria were present: echocardiographic image quality too poor for 2D-speckle tracking criteria, acute coronary events during follow-up, any changes in heart failure medication during follow-up unrelated to the study, and difference in rhythm at baseline and follow-up echocardiographies.The study was performed according to the declaration of Helsinki. All patients provided informed consent. The study was approved by regional Danish committee of health research ethics  — Protocol approval no. H-18,044,908 and by the Danish Data Protection Agency — approval no. VD-2018-453.Patients in the control group continued standard medical treatment. In addition to the standard treatment patients in the intervention group were educated in intake of a potassium rich diet and commenced oral potassium supplement and/or MRA (spironolactone or eplerenone) according to the POTCAST protocol . Because+, p-Na+, p-Mg2+, p-Ca2+, and p-creatinine and of the blood pressure. Repeated echocardiography was scheduled as soon as possible after either target p-K was met, or maximum dose of study medication was reached. Patients allocated to the control group were scheduled to repeated echocardiography six weeks after baseline due to preliminary results from the POTCAST trial showing that it takes six weeks on average to reach target p-K of 4.5-5.0 mmol/l. P-K and blood pressure were measured immediately after the follow-up echocardiography in both groups. The follow-up echocardiography was scheduled approximately at the same time of day as the baseline echocardiography in order to reduce variance caused by circadian changes in volume status, blood pressure and p-K as well as variation caused by the pharmacokinetics of the patients’ other daily medication.Transthoracic echocardiography was performed at enrollment after measurements of p-KAll echocardiographies were performed by a single investigator using the same ultrasound system , the same probe  and the same analyzing software . Cine loops from 3 standard apical views  were recorded using gray-scale harmonic imaging and saved in raw data format. Images were obtained at an acquisition rate of 50 to 90 frames per second. Left ventricular end-diastolic and end-systolic volumes and left ventricular ejection fraction (LVEF) were obtained using Simpson’s biplane method. For 2D-speckle tracking analysis, the inner endocardial borders were traced in the end-systolic frame in images from the three standard apical views. Speckles were tracked frame by-frame throughout the left ventricular wall during the cardiac cycle and basal-, mid-, and apical regions of interest were drawn Fig. . SegmentOff-line image analyses were independently performed by two investigators blinded to randomization allocation, clinical data and blood test results to reduce the risk of bias.The predefined outcomes were differences in changes from baseline to follow-up between the two groups in 2D-speckle tracking derived indices of systolic function: GLS, MD and for assessment of diastolic function: E/A, e´ and E/e´.A subgroup analysis was performed on patients in the intervention group that only received dietary guidance and potassium as a supplement to reach target p-K levels to test if the effects of increasing potassium levels on myocardial function was independent of the effects of MRA on loading conditions.2 values obtained from the final models. Interobserver variations was estimated as Single Score Intraclass Correlation. Analyses were done using a standard statistical software program (R version 4.1.0).Values are summarized as mean (standard deviation) or median (interquartile range). Continues data of normal distribution were compared using students t-test. Within-individual comparisons between baseline and follow-up echocardiographies were performed using the paired t-test. Fisher’s Exact test was used to compare categorical variables. Mean difference in changes was calculated as the between group difference in paired estimates to control for random differences in baseline measurements. Thus, the presented results represent absolute changes between study groups. Estimated differences are presented with 95% confidence intervals (95%CI). General linear models were used to assess the correlation between p-K and echocardiographic measurements and presented with RTo detect a clinically meaningful difference in changes in GLS of 1% with a standard deviation of 1.5 and with a two-tailed α = 0.05 and 1-β = 0.8 in a 1:1 randomization design, 21 patients in each group were needed. A total of 50 patients were included to account for potential dropouts.Fifty patients with low normal to moderately reduced LVEF were randomized: 26 patients to the intervention group and 24 to the control group. The participants had a mean age of 58 years SD 14) and 81% were male. The mean p-K was 3.95 mmol/l (SD 0.19), mean LVEF was 48% (SD 7), and mean GLS was − 14.6% (SD 3.1%). Baseline clinical history, medication, blood test results, and echocardiographic parameters were similar in the two groups  and mean dose of MRA of 23 mg. The mean difference in changes in p-K was 0.52 mmol/l , P < 0.001 higher in the intervention as compared to the control group.The follow-up echocardiography was performed after a mean of 44 days (SD 18) after baseline, 47 days (SD 17) in the intervention group and 40 days (SD 18) in the control group P = 0.22). Three patients were excluded from the final analysis: two due to poor image quality and one due to differences in rhythm at baseline and follow-up  — Fig. 2. Three At follow-up, the intervention group had improved myocardial longitudinal contraction measured by GLS with a mean difference in changes of -1.0% -2.0; -0.02), P < 0.05 compared to controls Fig. . No sign.0; -0.02The intervention group had improved diastolic function as measured by e’ with mean difference in changes of 0.9 cm/s , P = 0.04 and improvement in E/e’ with mean difference in changes of -1.5 , P = 0.03 compared to controls. No significant difference in changes was found between groups for E, A, or E/A.2 = 0.04), e’  or E/e’ . Models were adjusted for baseline values of p-K to account for regression to the mean. No association was found between GLS and change in systolic blood pressure , change in diastolic blood pressure , or change in heart rate  in linear models.In multiple linear regression models, no correlation was found between p-K and any of the echocardiographic parameters that were improved with the intervention. GLS  had similar baseline characteristics as the control group  has been associated with impaired systolic and diastolic responses to stress tests with epinephrine and increased preload . PotassiIn exploratory analysis of a subset of 131 patients from the TOPCAT trial, there was a trend towards improvement of Longitudinal Strain in patients treated with spironolactone  . AdditioThe protective effects of high potassium intake on cardiovascular outcomes have been reported in several studies. The potassium-induced lowering effect on blood pressure in hypertensive patients and reduction in the risk of strokes is particularly well documented , 6. RandTo our knowledge this is the first study to investigate myocardial function after actively increasing potassium levels in a randomized controlled setting. The study showed an improvement in GLS which has been repeatedly reported to be a strong predictor of arrhythmias , 29, andChanges in potassium concentrations in- and around the cardiomyocyte affect several aspects of myocardial electrophysiology which could result in altered mechanical function. P-K determines the resting membrane potential of the myocyte and significantly impacts depolarization velocity. Additionally, cardiac repolarization is mainly driven by an outward potassium flux and a low p-K lengthens the repolarization time and increases QT dispersion and active relaxation of the myocardium as well as the action potential- and refractory period durations . Thus, tThe effects of variations in potassium levels are likely to be more pronounced in patients with heart failure as the remodeling of the myocardium during deterioration of left ventricular function and increased hemodynamic load, even in early stages of heart failure, includes downregulation of potassium ion channels as well as of myocardial Na,K- ATPase concentration , responsPatients in the present study were increased from mid-normal to high-normal levels of p-K and there could be a greater improvement by increasing patients from low or even hypokalemic levels to high-normal levels. These considerations are left for future studies. Studies with hard endpoints are needed to elucidate if the present findings improve clinical patient outcomes.The randomized controlled design strengthens the causal inference of the findings. The present study was open labelled and therefore patients in the control group could have been motivated to increase their potassium intake independent of the trial. This is not likely to be an important factor as p-K levels in the control group were unchanged from baseline to follow-up. The study was limited by a low sample size and larger trials are needed to confirm the findings. Further, the study was designed as an all-comer trial of patients with low-normal- to moderately reduced left ventricular ejection fraction. Thus, the cohort is heterogeneous which could affect the generalizability of the results. The primary analysis is not conclusive on whether the effects seen with the intervention on myocardial function is caused by changes in potassium homeostasis per se or the effects of MRAs. However, the sensitivity analysis of patients only receiving potassium supplements showing similar results strengthens confidence in the main hypothesis.Targeting p-K between 4.5 and 5.0 mmol/l with dietary guidance on a potassium rich diet, oral potassium supplements and MRAs improved indices of systolic and diastolic left ventricular function in patients with low-normal to moderately reduced LVEF. These findings may in part explain previously reported beneficial effects of increased potassium intake and prove to be of clinical importance.Below is the link to the electronic supplementary material.Supplementary Material 1


To the best of our knowledge, the Cyberchondria Severity Scale-12 (CSS-12) has not been translated into Arabic; therefore, our objective was to assess the psychometric properties of the Arabic version of the CSS (CSS-12-Ar) among a sample of Lebanese adults.Participants were enrolled in January 2021. A confirmatory factor analysis (CFA) was carried out using the MPlus software v.7.2, reporting several goodness-of-fit indicators: Relative Chi-square (χ2/df), Root Mean Square Error of Approximation (RMSEA), Comparative Fit Index (CFI) and Tucker Lewis Index (TLI). To evaluate measurement invariance across gender, we conducted higher-order multiple group confirmatory analysis using lavaan software.2(50) = 173.34; p < 0.001; CFI = 0.926; RMSEA = 0.074 . The Cronbach’s alpha values were good for the total score (0.92), as well as for excessiveness (0.80), distress (0.77), reassurance (0.81) and compulsion (0.76). The results provided evidence of full scalar invariance across gender. The comparison of latent mean scores revealed no significant differences across gender, in either the cyberchondria total score or its facets. The CSS-12 score was positively associated with anxiety  , OCD  and stress  .449 participants enrolled in this study . Since the correlations between the four-factor model were very high (r > 0.8), we ran the higher-order CFA in which all first-order latent variables were loading a general factor. The analyzed model was well-fitted to the data χThe CSS-12-Ar was deemed a suitable scale to measure the severity of cyberchondria among Lebanese university students. We hope that researchers and clinicians can benefit now from this scale.The online version contains supplementary material available at 10.1186/s12888-023-05123-x. With the increasing impact of digital technology, subjects using the Internet as a source for health information is steadily increasing. In terms of prevalence, it is estimated that 62% of American adults search for health information online; thus constituting the fifth most common online activity . The numTo assess cyberchondria, McElroy and Shevlin developed the Cyberchondria Severity Scale (CSS-33 items) on a sample of 190 undergraduates . The CSSThe CSS is validated in multiple languages, including but not limited to Italian , TurkishA total of 449 adults agreed to enroll in this study. The mean age of the sample was 24.34 ± 8.22 years, with 70.6% females. The mean cyberchondria severity score was 15.91 ± 9.64. Table This is a cross-sectional study that was conducted during the COVID-19 pandemic (January 2021) through an online questionnaire. The total amount of participants was 449 individuals. A snowball sampling method was used to collect participants from all Lebanese governorates . The survey was completely anonymous and was distributed via the Whatsapp social application. Individuals above the age of 18 and residents of Lebanon were included .A minimal sample of 240 participants was deemed necessary to validate the CSS-12 scale, based on 20 participants per 1 scale item .The language of the questionnaire was Arabic, the official language of Lebanon. The questionnaire consisted of a sociodemographic section and different scales:Information about age, educational level, marital status, number of children, household crowding index (according to the number of rooms in the house excluding bathroom(s) and kitchen relative to the number of residents ) was colThe CSS in a brief 12-item version assessed compulsion, distress, excessiveness and reassurance, without the mistrust of medical professional dimension . The forThe CSS-12 items are scored on a Likert-type scale ranging from “1 = never” to “5 = always”. Higher scores reflected higher cyberchondria. Four factors derive from this scale: Excessiveness, distress, reassurance and compulsion. The Cronbach’s alpha values for the four subscales in this study were as follows: 0.80, 0.77, 0.81 and 0.76 respectively. Permission to use the scale was obtained from Dr Eoin McElroy.We used the Lebanese Anxiety Scale (LAS-10) to assess the CSS-12 convergent validity since spending more time on the internet searching for health information (i.e. cyberchondria) is associated with higher anxiety according to previous findings . The LASThe BDS-10  assessesThe YBOCS assesses the severity of OCD. It includes 10 items rated from 0 to 4 indicating no symptoms to extreme symptoms. Higher scores reflected more severe obsessive-compulsive symptoms . The AraWe used the YBOCS and BDS-10 scales to assess divergent validity, since previous research emphasized the manifestation of obsessive-compulsive components in cyberchondria , 39 and No missing data was found in the database as all questions were required in the Google form. The Mplus v. 7.2 was used to conduct confirmatory factor analyses (CFA) of the CSS-12. Multiple indices of goodness-of-fit were described: the Root Mean Square Error of Approximation (RMSEA)  and the Comparative Fit Index (CFI)  . We usedThe statistical analysis was conducted on the SPSS software version 25. Reliability was checked using Cronbach’s alpha for all scales and subscales. The sample was normally distributed as verified by the skewness and kurtosis of the CSS score, which varied between − 1 and + 1 . These c2(50) = 173.34; p < 0.001; CFI = 0.926; RMSEA = 0.074 . Standardized factor loadings of this model are summarized in Fig. Since the correlations between the four-factor model were very high (r > 0.8), we ran the higher-order CFA in which all first-order latent variables were loading a general factor. The analyzed model was well-fitted to the data χThe Cronbach’s alpha values were good for the total score 0.92), as well as for excessiveness (0.80), distress (0.77), reassurance (0.81) and compulsion (0.76). The total item correlations varied between 0.63 and 0.78  , OCD  and stress  .The CSS-12 score was positively associated with anxiety  and males  in the total sample, t(447) = -1.01, p = 0.315.The results of the measurement invariance testing are presented in Table To the best of our knowledge, the Arabic version is the first validation of the CSS-12 in a language other than English. In terms of dimension assessment, the higher-order factor model showed acceptable fit indices. Although the original version showed four factors, the latent correlations between those factors turned out to be very high in our study (r > 0.8), suggesting that these factors almost measure the same component, with limited utility in practice in differentiating them from each other. Previous research also encountered such heightened latent correlations and attempted to account for them through the introduction of a bifactor . Such apThe internal consistency of the CSS-12-Ar was very good for the total scale and each factor alone. The alpha value was higher in the Arabic version for the total scale and factor 4, but lower for Factors 1, 2 and 3 compared to the English version . All valThe CSS-12-Ar total score was positively correlated with anxiety, in line with previous findings . CyberchWith the increasing use of the internet in Lebanon as in the world, access to health information is gradually increasing; therefore, it has become compelling to be aware of the potential health threats of cyberchondria and its evaluation tools. As a result, the current findings will help researchers develop measures to mitigate the harmful effects of cyberchondria, implement policies, and raise awareness about cyberchondria, particularly among at-risk individuals. As a result, future efforts may concentrate on improving systems for effective monitoring of internal discomfort and increasing ways to assist individuals in gaining a sense of personal control.Symptoms were self-report  and thus are subjective. In addition, recall bias might be present, which may have led to an overestimation of the answers given to some questions. Participants may have misunderstood some of the questions, which is a source of information bias. Additionally, a main reason for selection bias is the refusal rate and the fact that the sample was recruited via the snowball technique. In addition, most participants were females, single, with a university level of education, which limits the generalizability of the findings. Confounding bias might be present since some information about participants’ occupation and mental health disorders were not assessed. Content validity of the instrument and test–retest reliability of scale were not conducted. Research on different study groups  and taking this study limitations into consideration, are needed.Our goal in this study was to provide evidence of validity of the CSS-12-Ar, which was done by inspection of its factor, convergent, and divergent validity as well as evaluating its internal consistency. All postulated hypotheses were verified by our database. Consequently, researchers and clinicians can take advantage of the CSS-12-Ar to assess cyberchondria levels in Lebanon.Below is the link to the electronic supplementary material.Supplementary Material 1: Cyberchondria Severity Scale (CSS-12-Ar)


Triticum aestivum L. seeds. We observed the in vivo translocation of the C-dots inthe plant using confocal microscopy. We measured the root elongationand shoot length to assess the effect of C-dots on plant growth. Ourstudy revealed that the plants exposed to C-dots grew 2.5-fold fasterthan the control group, indicating that C-dots are promising nanofertilizersfor aggrotech and non-toxic fluorescent biolabels for in vivo applications.Through coaxial directink writing, we fabricated a core–shellmesh system for the controlled release of carbon dots (C-dots). Inthe core ink, we developed an ink formulation with tuned viscosityusing hydroxypropyl cellulose and polyethylene glycol to host C-dots.Polycaprolactone was employed as the main shell material, in combinationwith sodium alginate, to control the degradation rate of the shell.We investigated the degradation profile of the 3D-printed meshes andtracked the weekly release of C-dots in an aqueous medium by spectrofluorometry.We tested the efficacy of the C-dot release on plants by placing themeshes in transparent soil with  We fabricated core−shell meshesof C-dots throughdirect ink writing as a controlled release system for agriculturalapplications. In these proof-of-concept studies, C-dotswere applied to the crop growth media through the nutrient solution,13 seed priming,14 rootexposure,15 or spraying on the seeds.21 To be able to harness the desired propertiesof C-dots in agricultural settings, a scalable, biocompatible, andcost-effective delivery method should be devised. In such a timelymanner, there is an ongoing shift in the agricultural industry towardcontrolled release systems to prevent the excessive use of agrochemicals.23 The controlledrelease approach enables a long residence of these chemicals in thesoil, prolongs their shelf life, and offers ease of transport. Currently,most of the controlled release systems are in the particle form, andtheir design relies on the encapsulation of a chemical of interest—core—witha degradable polymer shell. This shell allows the delivery of thecore over a period of time and protects the core against environmentalfactors. However, the chemical fabrication routes to produce thesesystems require high-cost precursors, organic solvents, high temperatures,or a vacuum environment, thus generating a high carbon footprint.Additionally, achieving a consistent shell thickness and homogeneityhas been shown to be problematic.24 Comparedto the particulate systems, core–shell structures in the fiberform can contribute to the homogeneous distribution of active ingredients.25 Electrospinning, so far, has been a straightforward,room-temperature method to envelope fertilizers, pesticides, and herbicidesin this form.27 Nevertheless, electrospinningalso utilizes excessive amounts of organic solvents, and the fabricationof fibers with proper mechanical strength is still challenging dueto the limitation of the fiber diameter that can be produced via thismethod. The micron-sized fibers can only encapsulate a scarce amountof material; therefore, the reports on the applications of electrospunfibers in agriculture only cover short-term release studies .29The zero-dimensionalityof C-dots enables ease in absorption andpenetration through the cell wall, and their fluorescent behaviorprovides the ability to track their dispersion.32 we tuned its degradation rate by blending it with sodium alginate(NaAlg).33 For the core ink to host C-dotsand ensure compatibility with the shell ink, we systematically exploredtwo viscosity modifiers, hydroxypropyl cellulose (HPC) and polyethyleneglycol (PEG). We tracked the degradation profile of the printed meshesby measuring the electrical conductivity arising from Na+ ions upon degradation of the PCL/NaAlg shell. We analyzed the time-dependentdelivery pattern of C-dots based on their emission spectra by spectrofluorometry.The in vivo transport route of C-dots from the root to the stem throughthe vascular system in a model plant (Triticum aestivum L.) was evaluated by confocal microscopy. We visually investigatedand measured the root and shoot growth in lab-made transparent soil.Our work showed that the seeds exposed to C-dots displayed 2.5-foldfaster growth than the plant without any treatment. We demonstratedthe robustness of the meshes for storage and transportation by assessingtheir foldability and ability to carry loads through mechanical characterization.Our work suggests an effective and sustainable delivery method tostore, carry, and deliver C-dots in a stable environment. Moreover,tracking the uptake and translocation of C-dots through the planttissues confirmed their potential as highly effective tools for invivo bioimaging. This benchtop, room-temperature prototyping methodpresented here is scalable and eco-friendly for the fabrication offunctional, robust, and foldable agricultural textiles for controlleddelivery applications.Coaxial directink writing (DIW) offers a room-temperature processvia co-extrusion of the core and shell inks. This mechanical routegenerates minimum waste and produces robust fibers in the sub-mm/mmrange with loadings that are relevant to agricultural applications.In this work, through DIW, we printed meshes of core–shellfibers that encapsulated C-dots in a degradable shell. We focusedon polycaprolactone (PCL) for the shell formulation due to its biodegradability,mechanical strength, and flexibility. Since the slow degradation ofPCL can pose a challenge for controlled release applications,Mw, of 200,600, and 1000 g/mol) was purchased from Merck.HPC  was obtained fromAlfa-Aesar. NaAlg, chloroform, PCL pellets , citric acid, urea, phytagel, magnesiumchloride hexahydrate (MgCl2), Murashige and Skoog basalmedium, and Pluronic F127 were purchased from Sigma-Aldrich. Calciumchloride dihydrate  was obtained fromZAG Kimya. All chemicals and reagents were used without purification. T. aestivum L. seed (product no 1016) was purchasedfrom Tekfen Tarım. Deionized water was purified using a MilliQwater purification system (conductivity = 18.2 Ω).PEG with a 2 kDa molecular weight cut-off for 48 h. This method effectivelyreduces the presence of impurities below the molecular weight cut-off,including ions and small byproducts, while retaining the synthesizedC-dots within the tubing, thereby guaranteeing proper purification.The dispersed C-dots in the water were then collected and freeze-dried.A facile one-stepmethod was used to prepare C-dots by modifying the protocol developedby Vercelli.Figure S1). TheGaussian fitting curves demonstrated that the average diameter ofthe corresponding products was 22.5 nm . The UV–vis spectra were recorded on a Lambda 365 in the 200–700 nm wavelength range. Thefluorescence intensity measurements of C-dots were conducted at roomtemperature on a fluorimeter . Theemission spectrum was obtained by exciting the C-dots solution of0.05 mg/mL at 360, 380, and 400 nm using a slit width of 5 mm foroutgoing and incoming beams and measuring emission up to 700 nm. Ramanspectroscopy was performed on a LabRAM HR Evolution instrument  equipped with a He–Ne laser (wavelength633 nm) with an edge filter and a 600 g/mm grid. Prior to the spectralanalysis, the C-dot suspensions were cast and flattened on a cleansilicon wafer, and a 50× long working distance objective wasused to focus the laser on the samples with a laser power of 0.29mW.Transmission electron microscopy  was used to analyze the morphology and sizedistribution of the as-prepared C-dots. Image acquisition was carriedout with Velox software. The TEM image analysis was performed usingImageJ . The particle size and size distribution were determined by averagingmore than 50 particles. The particle size of the C-dots was in therange of 10–50 nm  for 5 h at room temperature. For the firstcore ink, we fixed the amount of C-dots to 0.1 mg in 1 mL of deionizedwater and analyzed the addition of PEG200 (3–20 wt %) and HPC(5–35 wt %) to this aqueous suspension. The optimum formulationcontained 0.071 g (5 wt %) of PEG200. The PEG–C-dot mixturewas slowly stirred (∼300 rpm) for 1 h, and 0.36 g (25 wt %)of HPC was introduced afterward, and the stirring continued for another7 h until an entirely homogeneous mixture was obtained. For the secondcore ink, we dissolved 0.1 mg of C-dots in 1 mL of deionized waterand added HPC in the range of 5–35 wt %. Based on the printingperformance, the optimum amount of HPC was 0.43 g, corresponding toan addition of 25 wt %. This mixture was kept under magnetic stirringfor 8 h at room temperature.–1 and changed the strain from 0.01 to 1000%to find the range of the linear viscoelastic region. In the steady-statetests, the shear rate ranged from 0.01 to 1000 s–1.The rheologicalanalysis of the inks was carried out using a rheometer with a coneplate geometry of 25 mm/2° and a fixed gap size of 0.103 mm . In a dynamic regime, we set the frequency to 10rad s3 print cartridges equipped with a 15/19-gaugestainless steel metal coaxial nozzle. Prior to the printing, Repetier-Host and Slic3r as a slicingengine were used to convert the pre-prepared STL files into the geometry-code(G-code) file. The grid infill pattern was selected to generate amesh structure. The printing head moved in the X and Y directions, and the stage moved in the Z direction. The printing speed was kept constant at 1 mm/s, the infillpercentage was 8%, and the layer height was 0.2 mm. The distance betweenthe Teflon surface and the nozzle tip was fixed at approximately 0.1mm to prevent potential sagging and buckling due to the gravitationalforce.All inks were printed via apneumatic bioprinter in a coaxial configuration onto a Teflon surface to ease the removalof meshes at room temperature. The inks were gently mixed and loadedinto 3 cmFigure S2). We investigated thetranslocation and uptake of C-dots via confocal microscopy  with 10×/03 and 20×/0.8M27 dry objectives. Images were captured by using Zen imaging software.The plants were exposed to C-dots for a duration of 15 days. On day16, the plants were carefully harvested and dissected into their respectivetissue parts , which were then placedin a confocal Petri dish and sequentially excited at 405, 488, and561 nm to validate whether C-dots are capable of accumulating withinthe tissues of plants compared to the control group.We analyzed the core–shell structureof the 3D-printed meshes through field emission scanning electronmicroscopy . After drying, theprinted samples were physically fractured to visualize the core–shellstructure. The samples were fixed onto specimen stubs with a 90°angle to capture the cross-sectional fracture surface. To preventcharging, the samples were coated (∼9 nm) with Au/Pd by usinga Cressington 108 sputter coater at a current of 40 mA for 30 s. Thecore and shell thickness of the printed meshes were estimated usingImageJ. The 3D-printed meshes were photographed by a Spot InsightQE camera  at 5×and 10× magnifications in optical microscopy  . The degradation rate of each mesh was evaluated using eq Wo and Wt are the weights (g) of the meshes before andafter degradation, respectively.The hydrolyticdegradation profile of the PCL/NaAlg shells was obtained by immersingthe PCL/NaAlg shells in centrifuge tubes  containing 40mL of deionized water for 4 weeks by running three replicates. Themeshes in the aqueous solution in the centrifuge tube were removedgently by tweezers. We provided a controlled environment (a fixedtemperature of 21 °C with 79% humidity) for drying of mesheson the benchtop and avoided using excessive heat or rapid drying methods,as they may induce structural damage to the meshes. We regularly monitoredthe drying process to ensure that it was progressing as intended,and we checked for any signs of deformation, distortion, or qualityissues during the drying phase. After 6 h, we weighed the meshes.Subsequently, the remaining meshes were placed into the aqueous solutionsafter the experiment was concluded. Meshes were collected and driedat weekly intervals, and the changes in their weight were trackedas a function of immersion time . This conductivity level was accompanied by a weight changein the PCL/NaAlg structure over a 4 week period, with a total decreaseof 0.14 g . To assess the permissible exposure of Na+ ions in the soil, the United States Salinity Laboratory (USSL)has established a classification system based on the electrical conductivityof the saturation extract (ECe) values. The measured value of 491μS/cm is well below the threshold for level-1  classification.36 Therefore,we concluded that there will be no adverse impact on the soil at theobserved conductivity level. The thermal degradation behavior of thePCL/NaAlg shells with 2.5, 5.73, and 9.5 NaAlg wt % was also trackedby thermal gravimetric analysis  toexamine the effect of different NaAlg wt % on the degradation behavior.Samples were cut from the 3D-printed PCL/NaAlg shell (40 mg) and heatedto 1000 °C at 25 °C/min under a 30 mL/min nitrogen flow.Simultaneously, an electricalconductivity meter (WTW inoLab 720) was used each week to measurethe conductivity of released ions in the aqueous solution. The meshin the aqueous solution in the centrifuge tube was carefully takenby using tweezers and placed on a sterilized Petri dish. The remainingaqueous solution was filtered with sterilized filter paper and transferredto a beaker, which was previously washed with isopropanol. To ensurefull mixing of the precipitated ions, the aqueous solution in thebeaker was mixed with a sterilized magnetic stirrer at 300 rpm for5 min. Subsequently, we utilized an electrical conductivity meterand after the experiments were concluded, meshes were transferredto the aqueous solutions. The overall electrical conductivity  was attributed to the release of Naexc is 350 nm). After each measurement, themeshes and aqueous solutions in the fluorimeter cuvettes were transferredto the centrifuge tubes.The release profile of the C-dots was estimated throughspectrofluorometry  using Fluoraclesoftware. The PCL/NaAlg shell with two different core inks, HPC/C-dotsand HPC/PEG/C-dots, were immersed separately in centrifuge tubes containing40 mL of deionized water for 4 weeks under ambient conditions by runningthree replicates of each. Per week, these meshes were gently collectedusing tweezers, and the aqueous solution in centrifuge tubes was mixedwith a magnetic stirrer (∼300 rpm) for ∼5 min. Subsequently,all solutions were filtered with 0.45 μm pore size syringe filters(Sigma-Aldrich) and transferred to the fluorimeter cuvettes (Sigma-Aldrich)to monitor the weekly change in the emission intensity of the releasedC-dots as a function of the emission wavelength. Emission spectrawere obtained by monitoring the wavelength range of 370–700nm .The bending specimens with different layers  were printedin dimensions of 50.8 mm × 12.7 mm, having thicknesses less than1.6 mm, with a span of 24.6 mm. The test used a 1 mm/min crossheadmotion rate with 10 kN applied force. Additionally, we monitored theload-bearing capacity of the meshes. The meshes were fixed on thebending mandrel fixtures with tape, standard weights in the rangeof 10–500 g were gently placed onto the meshes, and the abilityto withstand loads of different layers of meshes was observed. Tensiletests were performed according to the ASTM D638 standard using a Zwickmechanical tester . 10, 14.23, and20 wt % PCL with 5.73 wt % NaAlg were cast into an ASTM D638 standarddog-bone-shaped mold and dried at room temperature for 24 h. The 37 A 1:4 mixture of NaAlg and phytagel was dripped into aMgCl2 solution with a polymer concentration of 1.2 wt %,and hydrogel-based transparent spherical beads were generated. A Murashigeand Skoog basal medium solution was prepared using deionized water,and spherical beads were placed in this nutrient solution for 24 h.Then, the solution was filtered out, and the beads were collected.The transparent soilwas synthesized via the procedure described by Ma.35 The absorption spectrum further demonstrates that the C-dotspossess higher absorption capacity in the UV range (200–400nm) when compared to chloroplasts. In contrast, C-dots demonstrateminimal absorption between 400 and 700 nm. This observation substantiatesthat the incorporation of C-dots enhances the absorption of UV lightby chloroplasts, without impeding the absorption of visible light.Consequently, this facilitation of UV light absorption promotes theenhancement of light conversion efficiency. As-prepared C-dots exhibitedan excitation-dependent emission behavior, with a red shift observedin emission wavelengths as the excitation wavelength was increased.The Raman spectrum showed two distinct Raman bands at 1300 and 1580cm–1, which can be attributed to sp3 defects(D-band) and sp2 carbon (G-band) in the synthesized N-dopedC-dots. The D-band represents the vibrations of carbon atoms withdangling bonds on the disordered graphite termination plane. On theother hand, the G-band corresponds to the E2g mode of graphite,indicating vibrations of sp2 carbon atoms in a two-dimensionalhexagonal lattice. The peak intensities of the D-band and G-band weremarked as ID and IG, respectively. The measured intensity ratio (ID/IG) for the synthesizedN-doped C-dots was approximately 1.2, suggesting the presence of agreater number of defective surface sites, which can be attributedto N doping. Additionally, the fluorescence observed in the synthesizedC-dots can be assigned to the surface defects that trap the excited-stateenergy. These defects play a significant role in the emission propertiesof the C-dots, contributing to their distinctive fluorescence characteristics.In 38 poly(glycolic acid) (PGA),39 and PCL40 are preferredfor long-term degradation due to their higher hydrophobicity. Amongthese, PCL exhibits better mechanical properties,41 and degradation products of PCL are generally non-hazardousand they do not pose significant risks to soil organisms or ecologicalsystems.43 However, the degradation of PCL in the pristineform was shown to take about 2–3 years, depending on the degradationmechanism.44 The degradation rate of PCL canbe tuned by utilizing natural additives that increase the water uptakeof PCL such as gelatin,45 chitosan,46 and NaAlg.47 We havechosen NaAlg to adjust the degradability of PCL due to its straightforwardprintability at room temperature and solubility in water without additionalprocessing steps.In this work, we aimed to produce a mesh systemthat is degradable, flexible, and mechanically robust to deliver C-dots.To ensure the proper printing and encapsulation of C-dots in a degradableshell, core and shell inks should be able to produce continuous fiberswithout clogging the nozzle. Degradable polymers such as poly(lacticacid) (PLA),T. aestivum L. in transparent soil. The details ofthe non-optimal PCL/NaAlg mixtures are provided in Table S1.We examined the rheology and printabilityof the inks that are composed of PCL and NaAlg in the range of 13–20and 1.5–8 wt %, respectively. We determined the lower and upperlimits of the PCL content based on the printing performance of thePCL and NaAlg mixture. Formulations that contain over 20 wt % PCLled to viscosities that required pressures that were above the printingcapabilities of our 3D printer, while those with a PCL content below13 wt % did not generate self-supporting and homogeneous fibers. Weset the lower limit of NaAlg based on the printability and the minimumrequired amount that can accelerate the degradation rate of PCL. Incontrast, the upper limit was based on reducing its detrimental effectson the mechanical properties of the mesh and the extrudability ofthe shell ink. A PCL-to-NaAlg ratio of ∼2.5:1 (14.32 wt % PCLand 5.73 wt % NaAlg) produced soft, continuous, robust, and highlyuniform fibers without clogging the nozzle during printing 2. The pr21 A viscosity modifier, PEG, was added at increasing amounts to thisaqueous solution to tune the viscosity and ensure compatibility withthe shell. PEG is known to improve the solubility of C-dots in aqueoussolutions49 and in alignment with the previous reports,45 PEG200 exhibited a better printing performancecompared to higher molecular weights (600 and 1000), which hinderedthe flow and clogged the nozzle. After evaluating the printing performanceof various weight percentages of PEG200 (3–20 wt %) in theC-dot/PEG200 solution, we selected a C-dot/PEG200 ratio of 1:7.25(0.69–5 wt %). However, ∼1 h after printing, the printedmesh structure of C-dot/PEG200 failed to preserve its shape due tothe swelling of the mesh. Consequently, an alternative viscosity modifier,HPC, was introduced to the core ink in the range of 5–35 wt% to adjust the viscosity. HPC alone also achieved a consistent flowwithout swelling at 30 wt %, and it exhibited better mechanical integritythan the one with PEG. Therefore, we opted out to demonstrate twocore ink systems, (i) C-dots/HPC/PEG200 and (ii) C-dots/HPC, in ouranalysis  and lossmodulus (G″) of the inks were measured at25 °C, and the intersection  was defined as the yield stress. The yield stress pointwas used to determine the critical condition for shear flow during3D printing. The yield stress of PCL/NaAlg, C-dots/HPC, and C-dots/HPC/PEG200was 678.9, 3589.3, and 1865.8 Pa, respectively (shown by arrows in eq P (Pa)is theapplied pressure, LC (m) is the lengthof the inner nozzle, and r (m) is the core nozzleradius.The rheological response of the optimizedinks wasevaluated bymeasuring their apparent viscosity, yield stress, storage, and lossmoduli. Expectedly, the viscosity of the inks decreased with an increasingshear rate and exhibited shear thinning behavior 2a. The f–9 to 50 × 10–9 Pa for the core and from ∼14 × 10–9 to ∼36 × 10–9 Pa forthe shell until the sudden release of the ink) in the process, thestrut diameters were enlarged. In contrast, with the increasing speedof the nozzle (from 1 to 5 mm/s), the inks came out as droplets, andthe strut diameter decreased. Therefore, to obtain a homogeneous strutdiameter, we maintained a constant nozzle speed of 2 mm/s, while theapplied pressure was fixed to ∼36 × 10–9, ∼21 × 10–9, and ∼14 ×10–9 Pa for C-dots/HPC, C-dots/HPC/PEG200, and PCL/NaAlg,respectively.The yield stress of all inks was below the maximum shearstressat the nozzle wall. The rheological behaviors of inks can substantiallyaffect their printing performance. Shear thinning limits the entanglementof polymer chains and enables the ink to flow easily with less resistanceat higher shear rates. Therefore, we estimated the printing parameters based on the rheological characterizationof the optimized inks to eliminate possible defects  during printing. The pneumaticpressure and nozzle speed were coordinated synchronously to delivercontinuous filaments and fixed strut diameter. With increasing pressure. The PCL/NaAlg meshes demonstrated ∼45wt % degradation after a 4-week period in natural soil .To assessthe influence of the environment on the degradation of polymer shells,two different media were employed to investigate the release patternof C-dots, deionized water, and lab-made transparent soil. In thepresence of water, NaAlg undergoes swelling, creating additional spaceand pathways within the PCL matrix where water molecules can furtherpermeate the structure.53 The spectrofluorometry recorded the emissionintensity of the released C-dots as a function of emission wavelengthto analyze the release profile of C-dots for 4 weeks. Normalized emissionintensity spectra showed a broad emission peak with a λmax around 440 nm (λexc with 350 nm) for allsamples from week 1 (W1) to 4 (W4)  5. The ina and b  in the blue light region (400–500nm). Combined with the absorption spectrum of C-dots in 50 Moreover, previous studies51 have reportedthe effective ability of C-dots to enhance the separation efficiencyof photogenerated electron–hole pairs and facilitate the rateof electron transfer, ultimately leading to improved photosynthesis.The emission spectra of C-dots, released from theshell matrix,are depicted in a and b S14 in thT. aestivum L. was identified in vivo, through blue (410–507 nm), green(494–601 nm), and red (568–712 nm) luminescent emissionsfrom C-dots observed at 405, 488, and 568 nm excitation, respectively.The fluorescence signals from C-dots exhibited a strong correlationwith the images of T. aestivum L. tissues,demonstrating the effectiveness of fluorescent labeling and the translocationof C-dots. The blue, green, and red fluorescent channels consistentlyexhibited stronger fluorescent intensity at the edges and relativelyweaker intensity in the central regions of the taproot, lateral roots,and stem across both samples. This observation was attributed to theaccumulation of C-dots in these areas. The notable distinction observedwas that the plant cultivated with the C-dot/HPC/PEG200 mesh exhibiteda higher signal intensity . Such difference in thefluorescence signal can be due to the enhanced stability and betterdispersion of C-dots facilitated by the presence of PEG200. PEG isa hydrophilic polymer with excellent solubility in water and otherpolar solvents and is recognized for its ability to improve the solubilityand dispersibility of C-dots in aqueous solutions.49 When PEG is added to a C-dot dispersion, it would act as a stabilizingagent and prevents the aggregation or agglomeration of C-dots. PEGmolecules form a protective layer around the C-dots, contributingto particle stability due to a steric hindrance. This steric stabilizationeffect inhibits the C-dots from coming into close contact and forminglarger aggregates. As a result, the C-dots remained dispersed andwell-distributed within the medium. Moreover, through confocal microscopyanalysis of the neat plant (plant with no treatment), only a few greenand red fluorescence signals were detected, exhibiting a patchy distributionpattern. Conversely, no fluorescence signal was identified in theblue fluorescence channel ,indicating a probable occurrence of autofluorescence originating fromthe T. aestivum L.56 Overall, thesamples containing C-dots demonstrated strong fluorescence signals,indicating a well-distributed presence of C-dots within the taproot,lateral roots, and stem of T. aestivum L.Dueto their water solubility and size, C-dots can transport easilyin an aqueous environment. Combined with their dispersibility, throughthe capillary effect, they are able to diffuse into the growing plantbody. Plants were exposed to 0.1 mg/mL C-dots, and the translocationof C-dots was tracked using confocal microscopy with three replicates.Essentially, over a 15-day period, the degradation of PCL/NaAlg shellmeshes, which contained the C-dots/HPC and C-dots/HPC/PEG, resultedin the release of C-dots into the soil. On day 16, plants were dissected,separating the tissues to the taproot, lateral roots, and stem, whichwere placed individually on confocal Petri dishes for examination.The uptake of C-dots by ntensity 6a in comTable S4. Plants treated with C-dots/HPC and C-dots/HPC/PEG200 grew ∼12and ∼13 cm in 15 days, respectively, while Ct-1 (plant withno treatment) had the lowest shoot length of ∼5 cm, which underlinesthe boosting effect of C-dots on plant growth. Additionally, seedswere separately treated with the meshes without C-dots to observethe effects of each polymer on plant growth. Out of all the mesh treatments,Ct-3 (HPC/PEG200) resulted in the longest shoot lengths, reaching∼9 cm, which is still 1.4-fold shorter than the plant thatwas treated with C-dots. On the other hand, when the core materialswere separated, Ct-6 (PEG200) exhibited a growth of ∼7 cm,while Ct-5 (HPC) displayed ∼5 cm. This suggests that the co-existenceof PEG200 and HPC in the core have promoted plant growth. Treatmentwith a mesh containing a shell formulation Ct-4 (PCL/NaAlg) showeda shoot length of ∼5.5 cm, and the shoot length of Ct-2 (PCL/NaAlg-HPC/PEG200)was slightly longer, ∼6 cm. Overall, we concluded that thepresence of C-dots elevated plant growth between 1.4- and 2.5-foldcompared to the control groups, and in alignment with previous reports,60 the presence of PEG, HPC, and NaAlg also contributed to the growth.The degradation rateof polymers and the effectof released C-dotson plant growth were correlated with the shoot and root length ofthe plant (cm). Each treatment group comprised three replicates, whereineach individual replicate corresponded to an independent plant subjectedto its respective treatment condition. Descriptive statistics, encompassingboth means and standard deviations, were computed for each treatmentgroup, focusing on the measured shoot length across a span of 15 days.The mean shoot length values for plant groups exposed to C-dots-HPCand C-dots-HPC-PEG200 were determined as 13.4 ± 0.52 and 11.43± 4.46 cm, respectively. The mean values and standard deviationsof control plants are given in T. aestivum L. seedsin the presence of N-doped C-dots. These C-dots enhance light absorptionefficiency in chloroplasts, displaying higher UV absorption comparedto chloroplasts and minimal absorption in the visible range. As aresult, chloroplasts experience increased UV light absorption withouthindering visible light absorption, ultimately leading to improvedlight conversion efficiency. We monitored the uptake and distributionof C-dots in T. aestivum L. with confocalmicroscopy. Additionally, we measured the shoot length, revealingthat C-dots facilitated a 2.5-fold increase in growth compared toplants with no treatment. These findings demonstrated that C-dotscan serve as an effective nanofertilizer in agriculture. Moreover,C-dots enabled a non-toxic scheme to track chemical intake in a plantbody, thus confirming that C-dots can be a good candidate for non-toxicin vivo biolabel owing to their fluorescent properties. Overall, using3D printing technology, we successfully delivered C-dots and createdsub-mm fibers in a mesh form. This approach resulted in a robust yetflexible frame with 100% encapsulation efficiency and minimal wasteproduction . This eco-friendly encapsulationmethod has the potential to host other chemicals and generate agriculturaltextiles.In this work, we demonstrated a room-temperature,mechanical routefor the fabrication of a controlled release system for as-preparedC-dots through coaxial printing. We designed inks to encapsulate C-dotsin the core and offer a biodegradable shell to exploit the photosyntheticefficiency of C-dots for plant growth. The analysis of the degradationprofile of 3D-printed meshes showed complete degradation within approximately4 weeks when exposed to both water and natural soil environments,but when the meshes were in transparent soil, the degradation processoccured within a shorter timeframe, typically around 15 days. We exploredthe growth of


The median (25–75th percentile) total VFQ scores in the Phaco group before and at 2 months after surgery were 71.1 (62.4–80.6) and 79.4 (69.0–84.0), respectively. (p = 0.006). The median (25–75th percentile) total VFQ scores in the Phaco-TLO group before and at 2 months after surgery were 69.8 (55.3–78.6) and 74.7 (65.1–83.3), respectively. (p = 0.005). Glaucoma patients who underwent not only cataract surgery alone but also combined cataract surgery and MIGS exhibited significant improvement in the VR-QOL.This study examined glaucoma patients after undergoing combined cataract and minimally invasive glaucoma surgery (MIGS), microhook ab interno trabeculotomy and goniotomy with the Kahook Dual Blade (KDB), or cataract surgery alone, and it then evaluates their vision-related quality of life (VR-QOL) following the procedure. A total of 75 eyes of 75 consecutive glaucoma patients in this prospective cohort study underwent phacoemulsification (Phaco) or phaco and MIGS (Phaco-TLO) between October 2019 and March 2022. In all cases, the National Eye Institute Visual Function Questionnaire (VFQ-25) was used to evaluate the 20 eyes in the Phaco group and the 55 eyes in the Phaco-TLO group before and at 2 months after surgery. There was a significant increase in the visual acuity (logMAR) at 2 months post-operatively (Phaco group; 0.34 ± 0.10 to −0.07 ± 0.1,  When intraocular pressure (IOP)-lowering medications do not effectively decrease the IOP during treatments of glaucoma, surgical treatment is necessary . GlaucomIn addition to the major glaucoma therapy and surgery target of maintaining the visual field perception and visual acuity, these also help to preserve the Quality of Life (QOL) of patients. To quantitatively measure vision-related QOL (VR-QOL), a 25-item scale, the National Eye Institute Visual Function Questionnaire (VFQ-25), has been developed . There aIn the current study, we evaluated the VR-QOL in glaucoma patients after they underwent combined cataract and ab interno trabeculotomy (TLO), microhook ab interno trabeculotomy and goniotomy with the Kahook Dual Blade (KDB), or cataract surgery alone.Between October 2019 and March 2022 at Hiroshima University Hospital, Japan, a total of 75 consecutive glaucoma patients underwent phacoemulsification (Phaco) or phaco-trabeculotomy (Phaco-TLO). The Institutional Review Board of the Hiroshima University approved this study protocol (E-1790). All subjects provided written informed consent in accordance with the principles outlined in the Declaration of Helsinki. Furthermore, prior to enrollment and participation in this research study, all patients provided standard consent for the surgery.This prospective cohort study enrolled 20 patients in the Phaco group and 55 patients in the Phaco-TLO group. The National Eye Institute VFQ-25 scores were evaluated for changes between the results obtained before surgery and at 2 months after surgery. Visual field (VF) data were collected using program 24–2 of the Humphrey Field Analyzer (HFA) , with only reliable VF data utilized. During the analysis, HFA reliability criteria  were applied. Exclusion criteria included patients who were less than 20 years of age, had the presence of dementia, or a history of intraocular surgery. Patients were also excluded if there were conditions ranging from secondary glaucoma to uveitis or neovascular glaucoma. We also excluded the eyes of patients with a history of glaucoma surgery.The VFQ-25 was completed by patients both before and at 2 months after surgery. As previously mentioned, there were 12 subscales that the items were assigned to and which included general health and vision, the presence of ocular pain, the visual function for near and distance activities, the vision-specific social functioning, mental health, role difficulties, dependency, driving, and color and peripheral vision. Subscales scores ranged from 0 to 100 points, with the highest possible function or minimal subjective impairment defined as being 100. The VFQ-25 utilized in this study was the Japanese version of the questionnaire, but which included a few modifications that were completed to take into account the Japanese culture and lifestyle.Changes in the best corrected visual acuity , changes in the IOP, and changes in IOP-lowering medications score were used as the secondary endpoints. In order to evaluate the scores for the IOP-lowering medications, a single drug was defined as a score of 1 point while a combination of drugs and oral drugs was defined as a score of 2 points.Transient ocular hypertension was defined as a postoperative IOP elevation > 30 mmHg. Hyphema was defined as hemorrhages in the anterior chamber with niveau formation.®, Johnson & Johnson Vision, Irvine, CA, USA) was added into the anterior chamber in order to increase the visuality of the Schlemm’s canal after the cataract surgery. Subsequently, after tilting the patient’s head and microscope, the Hill lens  was placed on the cornea. After then identifying the location of Schlemm’s canal, the microhook  or the KDB  was inserted through the main incision. A nasal and inferior site incision was subsequently made between 120° and 180°. The degree of the incision and the type of antibacterial and anti-inflammatory eye drops were prescribed in line with the personal preferences of each of the surgeons. At the time of the initial surgery, all of the IOP-lowering medications were stopped, with the resumption of the medications at post-operative follow-up visits determined in accordance to the discretion of the surgeon.There were multiple surgeons who performed the surgeries, with all of the surgical methods generally the same. All cataract surgeries were performed using a temporal 2.8 mm corneal incision. The cataract instrument used was the Signature Pro , with the PCB00V (Johnson & Johnson) or XY1  intraocular lens then implanted in the capsular bag. Sufficient sodium hyaluronate  and a power of 80% (1-β), the pre-study power calculation determined that a sample size of 50 patients would be required in order to detect a median VFQ-25 composite score difference of 4 points in the Phaco-TLO group. Furthermore, these calculations indicated that in order to detect a median VFQ-25 composite score difference of 8 points in the Phaco group, a sample size of 15 patients would be required. Subsequently, we then calculated the median scores for each of the VFQ-25 subscales and the composite score. A Wilcoxon signed-rank test was used to compare the pre- and post-operative results. Determination of the significance of the comparison between the Phaco and Phaco-TLO groups was performed using a Mann–Whitney U test and chi-square test. All statistical analyses used JMP software, version 16 , with p = 0.002), while the IOP-lowering medications scores were 1.7 ± 0.3 and 2.7 ± 0.2, respectively (p = 0.002). For the visual field index, the values for the Phaco and Phaco-TLO groups were 83.5 ± 12.9% and 67.7 ± 27.1%, respectively (p = 0.048). There were no significant differences observed between the groups for age, gender, type of glaucoma, visual acuity, and mean deviation.Baseline patient data are presented in p = 0.16, 0.26, 0.29, Mann–Whitney U test).The comparison of the changes in the visual acuity before and at 2 months after the surgery for the IOP and IOP-lowering medications score are presented in p = 0.054 to 0.79) and postoperative (p = 0.056 to 0.80) VFQ-25 composite scores and each of the 12 subscales.In the Phaco group, there were two eyes, while there were six eyes in the Phaco-TLO group that exhibited post-operative transient ocular hypertension. In four eyes of the Phaco-TLO group, there was hyphema with niveau formation.This study evaluated the VR-QOL of glaucoma patients before and after undergoing combined cataract and MIGS. When comparisons between the Phaco and Phaco-TLO groups were conducted for values before and 2 months after surgery, there was significant improvement in the visual acuity noted in both groups. Furthermore, there was significant improvement in the Phaco and Phaco-TLO groups at 2 months after surgery for the composite score of VFQ-25.Several studies have examined the VR-QOL following glaucoma surgery. Hirooka et al.  evaluateAdditional studies that have investigated patients undergoing cataract surgery in which there were no ocular diseases with the exception of cataracts have also reported finding a significantly improved VFQ-25 score ,15. The Suzukamo et al.  investigThe local and systemic side effects associated with IOP-lowering medication are well known and through the reduction of the IOP, they help to improve the patient’s VR-QOL . As conjHowever, it should be noted that it has been reported by some investigators that in conjunction with a worsening of the glaucomatous visual field defects, there was also a decrease in the VR-QOL ,19,20. HIn our current study, there were some limitations. First, the VR-QOL evaluations were undertaken at 2 months after surgery. In one of our recent studies that investigated corneal higher-order aberrations (HOAs) and coma-like or spherical-like aberrations, we found that for up to 3 months after the Phaco-TLO procedure, these aberrations remained significantly increased from the baseline . Thus, tIn conclusion, after patients underwent combined cataract and ab interno TLO, microhook ab interno trabeculotomy, and goniotomy with the KDB, significant improvements in the VR-QOL were observed.


Subthreshold depression (sD) negatively impacts well-being and psychosocial function and is more prevalent compared with major depressive disorder (MDD). However, as adults with sD are less likely to seek face-to-face intervention, internet-based cognitive-behavioral therapy (ICBT) may overcome barriers of accessibility to psychotherapy. Although several trials explored the efficacy of ICBT for sD, the results remain inconsistent. This study evaluated whether ICBT is effective in reducing depressive symptoms among Chinese adults with sD.A randomized controlled trial was performed. The participants were randomly assigned to 5 weeks of ICBT, group-based face-to-face cognitive-behavioral therapy (CBT), or a waiting list (WL). Assessments were conducted at baseline, post-intervention and at a 6-month follow-up. The primary outcome measured depressive symptoms using the Center for Epidemiological Studies Depression Scale (CES-D). Outcomes were analyzed using a mixed-effects model to assess the effects of ICBT.d = 0.12) and at follow-up (d = 0.10), and with CES-D at post-intervention (d = 0.06), compared to the CBT group.ICBT participants reported greater reductions on all the outcomes compared to the WL group at post-intervention. The ICBT group showed larger improvement on the Patient Health Questionnaire-9 (PHQ-9) at post-intervention (ICBT is effective in reducing depressive symptoms among Chinese adults with sD, and improvements in outcomes were sustained at a 6-month follow-up. Considering the low rates of face-to-face psychotherapy, our findings highlight the considerable potential and implications for the Chinese government to promote the use of ICBT for sD in China. Subthreshold depression (sD), although the definition is too broad to be used, refers to having a higher score than a certain cut-off in self-rated depression scales or having 1–2 significant depressive symptoms; however, it fails to meet the Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria for major depression  is an online intervention that can overcome some limitations of face-to-face cognitive-behavioral therapy  explored ICBT's efficacy for sD, the results, especially regarding evidence on the long-term efficacy, remain inconsistent; some RCTs showed the superiority of ICBT over control conditions at follow-up, while others did not  was the most common mood disorder in China with a lifetime prevalence of 3.4% and 12-month prevalence of 2.1%; considering China's 1.4 billion population, which indicates that an exceptionally large number of people are affected by MDD  ICBT participants would demonstrate significant improvements in the measures of depressive symptom and other secondary outcomes when compared with control participants, and these improvements would be sustained at a 6-months follow-up; (2) there would be no significant difference between internet-based and face-to-face CBT for sD on the reduction of depressive symptoms and other secondary outcomes; and (3) the use of ICBT would be effective and acceptable for Chinese adults with sD.This study conducted a 3-group RCT to explore the efficacy of a clinician-guided ICBT compared with a group-based face-to-face CBT and a waiting list (WL) control group on sD. Study outcomes were assessed at baseline, immediately after the intervention, and at 6-month follow-up. However, there were only two assessment points for the WL group (i.e. baseline and post-intervention). Thus, there were no comparisons between the intervention groups and the WL group at 6-month follow-up. This trial received approval from the Medical Ethics Committee of Ningbo University  and was pre-registered (registration number: ChiCTR2100049671).Overall, 554 participants were consecutively recruited between April and December 2020 from the general population via WeChat public account and related websites. Among them, 329 met the study's inclusion criteria. Participants had to meet the following inclusion criteria: (1) be a Chinese resident, (2) have a smart device and internet access, (3) be 18 years or older, (4) obtain a score of ⩾16 on the Center for Epidemiological Studies Depression Scale (CES-D), indicating sD  Axis Disorders (SCID) to assess final eligibility. The exclusion criteria were: (1) meeting the DSM-IV criteria for a major depressive episode (MDE), bipolar disorder, or psychotic disorder, (2) Current or past (in the past month) participation in psychotherapy elsewhere, and (3) using illicit substances or consuming >3 standard drinks daily. Eligible participants were administered standardized questionnaires, including all measures, and provided their sociodemographic data. Participants were thereafter randomly assigned to the following groups: ICBT group (n = 110), CBT group (n = 110), or WL group (n = 109), stratified by sex, age, and presenting depression symptom severity (symptom severity was determined using CES-D scores).Potentially eligible participants were invited for the telephone-administered Semi-Structured Clinical Interview for DSM (Fourth Edition) (www.random.org). Allocation was concealed from researchers using sequentially numbered, sealed opaque envelopes. The SCID was conducted by clinical psychologists, blind to the participants' assigned group. Participants could not be blinded to their allocation; however they were blinded to the condition of the WL group, as a control condition. Participants who completed post-intervention and follow-up questionnaires received ¥50 CNY (approximately $7.50 USD).An independent research assistant completed randomization, according to a 1:1:1 ratio with a block size of six, using a computerized random number generator  ‘Would you feel confident in recommending this program?’ and (2) ‘Was it worth your time doing the program?’ To these questions, participants responded with either ‘yes’ or ‘no’  or Kruskal–Wallis tests for continuous measures and chi-square tests for categorical variables.All analyses were conducted using SAS version 9.4 . A two-tailed Participants in both ICBT and CBT groups who had not begun Lesson 1 were excluded from the analyses. The least-squares means (LS means) of outcomes were estimated, conducting an intention-to-treat (ITT) mixed-effects model for repeated measures  were based on the method suggested for mixed model analysis  = 13.35), 66.4% were women, and most participants were married (72.00%) and employed full-time (73.50%). Additionally, only 8.2% and 7.5% of the participants had an educational qualification higher than a certificate/diploma/university degree and a high-level income, respectively. Furthermore, nearly a quarter of the participants reported a history of MDE.s.d. for outcomes at baseline, post-intervention and at a 6-month follow-up for the three groups. The mixed-effects model analyses revealed significant time × group interactions on the CES-D , BDI-II , PHQ-9 , GAD-7  and RRS .p < 0.001), whereas WL participants showed a significant increase on the PHQ-9 (p = 0.043) and RRS (p < 0.001).Contrasts comparing change from baseline showed a consistent pattern of significant improvement at post-intervention and follow-up for both CBT and ICBT groups on all the outcomes (p < 0.001). The ICBT group showed significantly stronger improvement on the PHQ-9 at post-intervention (p < 0.001) and at follow-up (p = 0.015), and on the CES-D at post-intervention (p = 0.006) in comparison to the CBT group. No other significant differences between the CBT and ICBT groups were found.Contrasts revealed that both CBT and ICBT resulted in a significantly larger reduction on all the outcomes compared with WL at post-intervention and follow-up (d), calculated both within and between groups based on estimated means. The within-group effect sizes on the primary outcome measure CES-D were small for all treatments at post-intervention  and follow-up . The within-group effect size for CES-D for the WL group was 0.15 (95% CI 0.12–0.18) at post-intervention.d = 0.06, 95% CI 0.02–0.09; follow-up: d = 0.04, 95% CI 0.00–0.07), and between-group effect sizes for CES-D between the intervention groups and WL group ranged from small to large .The between-group effect sizes for CES-D between the CBT group and ICBT group were small  for the intervention groups. The between-group effect sizes for secondary outcomes were small .The within-group effect sizes for secondary outcomes ranged from small to large (post-intervention: CBT d range: 0.03–0.19), and the between-group effect sizes for secondary outcomes ranged from small to large  for the WL group.The within-group effect sizes for secondary outcomes were small (p < 0.001), while there were no significant differences between the CBT and ICBT group at follow-up (p < 0.001). We calculated the NNT at post-intervention with the WL group as the reference. The NNT to achieve one additional clinically significant improvement were 3.04 (95% CI 2.23–4.36) and 2.62 (95% CI 2.18–3.35) respectively for CBT and ICBT. The NNT to achieve one additional reliable change were 1.86 (95% CI 1.52–2.39) and 1.79 (95% CI 1.45–2.33) respectively for CBT and ICBT.s.d. = 3.35) and 3.76 (s.d. = 11.23), respectively. The mean total time spent with a clinical psychologist for each participant in the complete ICBT program was 31.08 min (s.d. = 21.94).The five lessons were completed by 83 of 102 ICBT participants (81.37%) and 55 of 85 CBT participants in 8 weeks (64.70%); the average number of lessons completed for ICBT, and CBT participants were 4.19 , 69/85 (81.18%), and 59/92 (64.13%) of ICBT, CBT, and WL participants, respectively. At a 6-month follow-up, data were collected from 83/102 (81.37%) and 58/85 (68.24%) of ICBT and CBT participants, respectively.The ICBT and CBT participants who completed the post-intervention satisfaction questionnaires reported a high level of satisfaction. Further, 80 ICBT participants (87.91%) and 47 CBT participants (68.12%) felt confident in recommending the intervention to others; while 76 ICBT participants (83.52%) and 49 CBT participants (71.01%) reported that the intervention was worth doing.Healthy Psychological Station, and >80% of them reported a high degree of satisfaction. Overall, ICBT is effective in reducing sD in Chinese adults.In this study, we examined the efficacy of clinician-guided ICBT on Chinese adults with sD, compared to a face-to-face CBT group and WL control group. We found that ICBT was effective from pre- to post-intervention and at a 6-month follow-up for depressive and anxiety symptoms, and rumination among adults with sD. In addition, over 30% and 60% of participants reported clinically significant improvement and reliable change for CES-D from pre-treatment to follow-up, respectively. Furthermore, 81.37% of participants completed the five lessons in the v. WL regarding reducing depressive symptom severity, was larger than that of two meta-analyses on ICBT for the treatment of sD (Reins et al., The findings of the present study are encouraging and consistent with the results in previous studies concerning ICBT for sD (Cuijpers et al., Significant and higher improvement on the RRS were observed in the ICBT group, compared to the WL group. Previous findings indicated that ICBT was an effective treatment for repetitive, negative thinking among patients with mixed anxiety and depression (Newby, Williams, & Andrews, et al.'s (v. CBT among adults with sD. Therefore, future research should use a larger sample to address this issue.ICBT participants showed significant improvement on the CES-D and PHQ-9 with small effect size at post-intervention and showed significant improvement on the PHQ-9 with small effect size at follow-up, compared to CBT participants. Furthermore, a higher proportion of ICBT participants experienced reliable change and clinically significant improvement for CES-D at post-intervention and follow-up, which may be because of higher adherence found among ICBT participants than CBT participants in our study; this concurs with Spek et al.'s  findingset al.'s , while tet al.'s . There wThis study focuses on improving sD, and to the best of our knowledge, is the first study to support the feasibility and acceptability of ICBT for the Chinese population with sD. The results are encouraging and consistent with previous studies examining the use of ICBT for adults with sD in western countries (Reins et al., Of the ICBT participants, 48.3% failed to achieve a reliable change at a 6-month follow-up. This may be because some ICBT participants reported that they experienced MDE. Researchers demonstrated that a history of MDE is one of the most common predictive factors for lack of treatment response (Andersson, Bergstrm, Hollndare, Ekselius, & Carlbring, First, the effects on self-reported depression severity were almost moderate in size, which further supports the potential benefits of ICBT in treating depressive symptoms in the early stage. Studies using ICBT to prevent depression demonstrated that the treatment of sD may reduce the severity of symptoms and help prevent further deterioration and the onset of full-blown major depression (Buntrock et al., This study presents the following strengths. First, participants' mental health status was measured using validated measurement tools with good reliability and validity. Second, attrition rates were relatively low at post-intervention and at a 6-month follow-up; the linear mixed model provided an unbiased estimation of the ITT effect when it was assumed that participant data lost-at-follow-up were randomly missing; Third, the study's randomized controlled design with the direct comparison of two active conditions. Finally, we recruited participants from the general population rather than general practice or clinics, and thus, no biases were caused by individuals' help-seeking behavior and doctors' recognition of the disease (Paykel et al., There are several limitations of our study. First, the results were based on participants' self-reported scores collected via the Internet, which could cause selection bias. Additionally, we relied on self-report measurements at post-intervention and follow-up and thus had no information regarding the diagnoses of depressive episodes during these stages. Second, most participants were better educated with higher income levels than the general Chinese population, which may help them learn more from ICBT (Imamura et al., This trial showed that ICBT is effective in reducing depressive symptoms among Chinese adults with sD, and the improvements in outcomes were sustained at a 6-month follow-up. Our study adds to existing literature indicating that ICBT, an intervention that requires less therapist time and may be more acceptable for adults with sD, may be a complement to face-to-face CBT in the treatment of sD. A large number of Chinese people are affected by sD, although the treatment rates of face-to-face psychotherapy for depression are low. Thus, the current study's findings further highlight the considerable potential of ICBT programs in improving online access to psychotherapy and producing reasonable symptom gains for these individuals, who may otherwise never receive mental health services.